3-149213737-G-T

Position:

• chr3-149213737-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000096.4(CP):​c.147-1039C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 151,962 control chromosomes in the GnomAD database, including 1,062 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.093 (1062 hom., cov: 32)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380

Genes affected

CP (HGNC:2295): (ceruloplasmin) The protein encoded by this gene is a metalloprotein that binds most of the copper in plasma and is involved in the peroxidation of Fe(II)transferrin to Fe(III) transferrin. Mutations in this gene cause aceruloplasminemia, which results in iron accumulation and tissue damage, and is associated with diabetes and neurologic abnormalities. Two transcript variants, one protein-coding and the other not protein-coding, have been found for this gene. [provided by RefSeq, Feb 2012]

CP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CP	NM_000096.4	c.147-1039C>A		intron_variant		ENST00000264613.11	NP_000087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CP	ENST00000264613.11	c.147-1039C>A		intron_variant		1	NM_000096.4	ENSP00000264613.6
CP	ENST00000490639.5	n.179-1039C>A		intron_variant		1
CP	ENST00000455472.3	c.267-1039C>A		intron_variant		5		ENSP00000426888.1
CP	ENST00000481169.5	n.147-1039C>A		intron_variant		2		ENSP00000418773.1

Frequencies

GnomAD3 genomes AF: 0.0930 AC: 14126 AN: 151844 Hom.: 1059 Cov.: 32

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0929

Gnomad OTH AF: 0.0976

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0930 AC: 14134 AN: 151962 Hom.: 1062 Cov.: 32 AF XY: 0.0994 AC XY: 7383 AN XY: 74258

Gnomad4 AFR AF: 0.0215

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0611

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.0929

Gnomad4 OTH AF: 0.0980

Alfa AF: 0.0638 Hom.: 91

Bravo AF: 0.0909

Asia WGS AF: 0.224 AC: 778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.15
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16861634; hg19: chr3-148931524;